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Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target

Prostate cancer (PCa) is the most frequently diagnosed cancer in men, causing considerable morbidity and mortality. The P2X4 receptor (P2X4R) is the most ubiquitously expressed P2X receptor in mammals and is positively associated with tumorigenesis in many cancer types. However, its involvement in P...

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Autores principales: He, Jiepei, Zhou, Yuhan, Arredondo Carrera, Hector M., Sprules, Alexandria, Neagu, Ramona, Zarkesh, Sayyed Amin, Eaton, Colby, Luo, Jian, Gartland, Alison, Wang, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699771/
https://www.ncbi.nlm.nih.gov/pubmed/33233569
http://dx.doi.org/10.3390/cells9112511
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author He, Jiepei
Zhou, Yuhan
Arredondo Carrera, Hector M.
Sprules, Alexandria
Neagu, Ramona
Zarkesh, Sayyed Amin
Eaton, Colby
Luo, Jian
Gartland, Alison
Wang, Ning
author_facet He, Jiepei
Zhou, Yuhan
Arredondo Carrera, Hector M.
Sprules, Alexandria
Neagu, Ramona
Zarkesh, Sayyed Amin
Eaton, Colby
Luo, Jian
Gartland, Alison
Wang, Ning
author_sort He, Jiepei
collection PubMed
description Prostate cancer (PCa) is the most frequently diagnosed cancer in men, causing considerable morbidity and mortality. The P2X4 receptor (P2X4R) is the most ubiquitously expressed P2X receptor in mammals and is positively associated with tumorigenesis in many cancer types. However, its involvement in PCa progression is less understood. We hypothesized that P2X4R activity enhanced tumour formation by PCa cells. We showed that P2X4R was the most highly expressed, functional P2 receptor in these cells using quantitative reverse transcription PCR (RT-PCR) and a calcium influx assay. The effect of inhibiting P2X4R on PCa (PC3 and C4-2B4 cells) viability, proliferation, migration, invasion, and apoptosis were examined using the selective P2XR4 antagonists 5-BDBD and PSB-12062. The results demonstrated that inhibiting P2X4R impaired the growth and mobility of PCa cells but not apoptosis. In BALB/c immunocompromised nude mice inoculated with human PC3 cells subcutaneously, 5-BDBD showed anti-tumourigenic effects. Finally, a retrospective analysis of P2RX4 expression in clinical datasets (GDS1439, GDS1746, and GDS3289) suggested that P2X4R was positively associated with PCa malignancy. These studies suggest that P2X4R has a role in enhancing PCa tumour formation and is a clinically targetable candidate for which inhibitors are already available and have the potential to suppress disease progression.
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spelling pubmed-76997712020-11-29 Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target He, Jiepei Zhou, Yuhan Arredondo Carrera, Hector M. Sprules, Alexandria Neagu, Ramona Zarkesh, Sayyed Amin Eaton, Colby Luo, Jian Gartland, Alison Wang, Ning Cells Article Prostate cancer (PCa) is the most frequently diagnosed cancer in men, causing considerable morbidity and mortality. The P2X4 receptor (P2X4R) is the most ubiquitously expressed P2X receptor in mammals and is positively associated with tumorigenesis in many cancer types. However, its involvement in PCa progression is less understood. We hypothesized that P2X4R activity enhanced tumour formation by PCa cells. We showed that P2X4R was the most highly expressed, functional P2 receptor in these cells using quantitative reverse transcription PCR (RT-PCR) and a calcium influx assay. The effect of inhibiting P2X4R on PCa (PC3 and C4-2B4 cells) viability, proliferation, migration, invasion, and apoptosis were examined using the selective P2XR4 antagonists 5-BDBD and PSB-12062. The results demonstrated that inhibiting P2X4R impaired the growth and mobility of PCa cells but not apoptosis. In BALB/c immunocompromised nude mice inoculated with human PC3 cells subcutaneously, 5-BDBD showed anti-tumourigenic effects. Finally, a retrospective analysis of P2RX4 expression in clinical datasets (GDS1439, GDS1746, and GDS3289) suggested that P2X4R was positively associated with PCa malignancy. These studies suggest that P2X4R has a role in enhancing PCa tumour formation and is a clinically targetable candidate for which inhibitors are already available and have the potential to suppress disease progression. MDPI 2020-11-20 /pmc/articles/PMC7699771/ /pubmed/33233569 http://dx.doi.org/10.3390/cells9112511 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
He, Jiepei
Zhou, Yuhan
Arredondo Carrera, Hector M.
Sprules, Alexandria
Neagu, Ramona
Zarkesh, Sayyed Amin
Eaton, Colby
Luo, Jian
Gartland, Alison
Wang, Ning
Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target
title Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target
title_full Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target
title_fullStr Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target
title_full_unstemmed Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target
title_short Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target
title_sort inhibiting the p2x4 receptor suppresses prostate cancer growth in vitro and in vivo, suggesting a potential clinical target
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699771/
https://www.ncbi.nlm.nih.gov/pubmed/33233569
http://dx.doi.org/10.3390/cells9112511
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